tbuckley/cabot-search huggingface dataset:
In large acute ischemic stroke, adding endovascular thrombectomy to medical therapy improved function at 90 d
Authors: Emma Ferguson, Eddy Lang
Journal: Annals of Internal Medicine (2023)

ACP Journal ClubJune 2023In large acute ischemic stroke, adding endovascular thrombectomy to medical therapy improved function at 90 dEmma Ferguson , MBBS, and Eddy Lang , MDEmma Ferguson , MBBSUniversity of Ottawa, Ottawa, Ontario, Canada (E.F.)Search for more papers by this author, and Eddy Lang , MDUniversity of Calgary, Calgary, Alberta, Canada (E.L.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/J23-0033 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationSarraj A, Hassan AE, Abraham MG, et al; SELECT2 Investigators. Trial of endovascular thrombectomy for large ischemic strokes. N Engl J Med. 2023;388:1259-1271. https://pubmed.ncbi.nlm.nih.gov/36762865Clinical Impact RatingsEmergency Med: Hospitalists: GIM/FP/GP: Neurology: References1. Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association [Editorial]. Stroke. 2019;50:e344-e418. [PMID: 31662037] Google Scholar2. Huo X, Ma G, Tong X, et al; ANGEL-ASPECT Investigators. Trial of endovascular therapy for acute ischemic stroke with large infarct. N Engl J Med. 2023;388:1272-1283. [PMID: 36762852] Google Scholar Author, Article, and Disclosure InformationAuthors: Emma Ferguson, MBBS; Eddy Lang, MDAffiliations: University of Ottawa, Ottawa, Ontario, Canada (E.F.)University of Calgary, Calgary, Alberta, Canada (E.L.)Disclosures: The commentators have reported no disclosures of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=J23-0033.This article was published at Annals.org on 6 June 2023.ACP Journal Club is editorially independent from Annals of Internal Medicine. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics June 2023Volume 176, Issue 6Page: JC65KeywordsCarotid arteriesCerebral arteriesComputed axial tomographyDisabilitiesInfarctionIntent to treat analysisIschemic strokeQuality of life ePublished: 6 June 2023 Issue Published: June 2023 Copyright & PermissionsCopyright © 2023 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Cash transfers save lives of women and children in poor countries, study finds
Authors: Janice Hopkins Tanne
Journal: BMJ (2023)

Cash transfers save lives of women and children in poor countries, study finds Janice Hopkins TanneDistributing money from the government to poor individuals or families in low and middle countries in the form of cash transfers saved the lives of women and children under the age of 5 in the first two years of the programme, a study has found.The findings, reported in Nature, 1 support the use of such programmes, which many countries introduced or expanded during the pandemic.
Accelerometer-measured intensity-specific physical activity, genetic risk and incident type 2 diabetes: a prospective cohort study
Authors: Mengyun Luo, Chenhao Yu, Borja Del Pozo Cruz, Liangkai Chen, Ding Ding
Journal: British Journal of Sports Medicine (2023)

Although 30 min/day of moderate-intensity physical activity is suggested for preventing type 2 diabetes (T2D), the current recommendations exclusively rely on self-reports and rarely consider the genetic risk. We examined the prospective dose-response relationships between total/intensity-specific physical activity and incident T2D accounting for and stratified by different levels of genetic risk.This prospective cohort study was based on 59 325 participants in the UK Biobank (mean age=61.1 years in 2013-2015). Total/intensity-specific physical activity was collected using accelerometers and linked to national registries until 30 September 2021. We examined the shape of the dose-response association between physical activity and T2D incidence using restricted cubic splines adjusted for and stratified by a polygenic risk score (based on 424 selected single nucleotide polymorphisms) using Cox proportional hazards models.During a median follow-up of 6.8 years, there was a strong linear dose-response association between moderate-to-vigorous-intensity physical activity (MVPA) and incident T2D, even after adjusting for genetic risk. Compared with the least active participants, the HRs (95% CI) for higher levels of MVPA were: 0.63 (0.53 to 0.75) for 5.3-25.9 min/day, 0.41 (0.34 to 0.51) for 26.0-68.4 min/day and 0.26 (0.18 to 0.38) for >68.4 min/day. While no significant multiplicative interaction between physical activity measures and genetic risk was found, we found a significant additive interaction between MVPA and genetic risk score, suggesting larger absolute risk differences by MVPA levels among those with higher genetic risk.Participation in physical activity, particularly MVPA, should be promoted especially in those with high genetic risk of T2D. There may be no minimal or maximal threshold for the benefits. This finding can inform future guidelines development and interventions to prevent T2D.
Lotilaner Ophthalmic Solution 0.25% for Demodex Blepharitis
Authors: Ian Benjamin Gaddie, Eric D. Donnenfeld, Paul Karpecki, Patrick Vollmer, Gregg J. Berdy, Jared D. Peterson, Blake Simmons, Aimée R.P. Edell, William E. Whitson, Joseph B. Ciolino, Stephanie N. Baba, Mark Holdbrook, José Trevejo, John Meyer, Elizabeth Yeu
Journal: Ophthalmology (2023)

To evaluate the safety and efficacy of lotilaner ophthalmic solution 0.25% compared with vehicle for the treatment of Demodex blepharitis.Prospective, randomized, double-masked, vehicle-controlled, multicenter, phase 3 clinical trial.Four hundred twelve patients with Demodex blepharitis were assigned randomly in a 1:1 ratio to receive either lotilaner ophthalmic solution 0.25% (study group) or vehicle without lotilaner (control group).Patients with Demodex blepharitis treated at 21 United States clinical sites were assigned either to the study group (n = 203) to receive lotilaner ophthalmic solution 0.25% or to the control group (n = 209) to receive vehicle without lotilaner bilaterally twice daily for 6 weeks. Collarettes and erythema were graded for each eyelid at screening and at all visits after baseline. At screening and on days 15, 22, and 43, 4 or more eyelashes were epilated from each eye, and the number of Demodex mites present on the lashes was counted with a microscope. Mite density was calculated as the number of mites per lash.Outcome measures included collarette cure (collarette grade 0), clinically meaningful collarette reduction to 10 collarettes or fewer (grade 0 or 1), mite eradication (0 mites/lash), erythema cure (grade 0), composite cure (grade 0 for collarettes as well as erythema), compliance with the drop regimen, drop comfort, and adverse events.At day 43, the study group achieved a statistically significant (P < 0.0001) higher proportion of patients with collarette cure (56.0% vs. 12.5%), clinically meaningful collarette reduction to 10 collarettes or fewer (89.1% vs. 33.0%), mite eradication (51.8% vs. 14.6%), erythema cure (31.1% vs. 9.0%), and composite cure (19.2% vs. 4.0%) than the control group. High compliance with the drop regimen (mean ± standard deviation, 98.7 ± 5.3%) in the study group was observed, and 90.7% of patients found the drops to be neutral to very comfortable.Twice-daily treatment with lotilaner ophthalmic solution 0.25% for 6 weeks generally was safe and well tolerated and met the primary end point and all secondary end points for the treatment of Demodex blepharitis compared with vehicle control.Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Profiling of purified autophagic vesicle degradome in the maturing and aging brain
Authors: Emmanouela Kallergi, Devanarayanan Siva Sankar, Alessandro Matera, Angeliki Kolaxi, Rosa Chiara Paolicelli, Joern Dengjel, Vassiliki Nikoletopoulou
Journal: Neuron (2023)

Autophagy disorders prominently affect the brain, entailing neurodevelopmental and neurodegenerative phenotypes in adolescence or aging, respectively. Synaptic and behavioral deficits are largely recapitulated in mouse models with ablation of autophagy genes in brain cells. Yet, the nature and temporal dynamics of brain autophagic substrates remain insufficiently characterized. Here, we immunopurified LC3-positive autophagic vesicles (LC3-pAVs) from the mouse brain and proteomically profiled their content. Moreover, we characterized the LC3-pAV content that accumulates after macroautophagy impairment, validating a brain autophagic degradome. We reveal selective pathways for aggrephagy, mitophagy, and ER-phagy via selective autophagy receptors, and the turnover of numerous synaptic substrates, under basal conditions. To gain insight into the temporal dynamics of autophagic protein turnover, we quantitatively compared adolescent, adult, and aged brains, revealing critical periods of enhanced mitophagy or degradation of synaptic substrates. Overall, this resource unbiasedly characterizes the contribution of autophagy to proteostasis in the maturing, adult, and aged brain.
Differential behavior-related activity of distinct hippocampal interneuron types during odor-associated spatial navigation
Authors: Thomas Forro, Thomas Klausberger
Journal: Neuron (2023)

Hippocampal pyramidal cells represent an animal's position in space together with specific contexts and events. However, it is largely unknown how distinct types of GABAergic interneurons contribute to such computations. We recorded from the intermediate CA1 hippocampus of head-fixed mice exhibiting odor-to-place memory associations during navigation in a virtual reality (VR). The presence of an odor cue and its prediction of a different reward location induced a remapping of place cell activity in the virtual maze. Based on this, we performed extracellular recording and juxtacellular labeling of identified interneurons during task performance. The activity of parvalbumin (PV)-expressing basket, but not of PV-expressing bistratified cells, reflected the expected contextual change in the working-memory-related sections of the maze. Some interneurons, including identified cholecystokinin-expressing cells, decreased activity during visuospatial navigation and increased activity during reward. Our findings suggest that distinct types of GABAergic interneuron are differentially involved in cognitive processes of the hippocampus.
Male sling is as good as more complex surgery for incontinence after prostate surgery
Authors: Helen Saul, Brendan Deeney, Samantha Cassidy, Jemma Kwint, Lynda Constable, Paul Abrams
Journal: BMJ (2023)

The study Constable L, Abrams P, Cooper D, et. Synthetic sling or artificial urinary sphincter for men with urodynamic stress incontinence after prostate surgery: the MASTER non-inferiority RCT. Health Technol Assess 2022;26:1-152 To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/male-sling-is-as-good-as-more-complex-surgery-for-incontinence-after-prostate-surgery/
Concurrent chemoradiotherapy followed by adjuvant cisplatin–gemcitabine versus cisplatin–fluorouracil chemotherapy for N2–3 nasopharyngeal carcinoma: a multicentre, open-label, randomised, controlled, phase 3 trial
Authors: Li-Ting Liu, Huai Liu, Ying Huang, Jin-Hao Yang, Si-Yi Xie, Yuan-Yuan Li, Shan-Shan Guo, Bin Qi, Xiao-Yun Li, Dong-Ping Chen, Feng Jin, Xue-Song Sun, Zhen-Chong Yang, Sai-Lan Liu, Dong-Hua Luo, Ji-Bin Li, Qing Liu, Pan Wang, Ling Guo, Hao-Yuan Mo, Fang Qiu, Qi Yang, Yu-Jing Liang, Guo-Dong Jia, Dong-Xiang Wen, Jin-Jie Yan, Chong Zhao, Qiu-Yan Chen, Rui Sun, Lin-Quan Tang, Hai-Qiang Mai
Journal: The Lancet Oncology (2023)
Comprehensive machine learning-generated classifier identifies pro-metastatic characteristics and predicts individual treatment in pancreatic cancer: A multicenter cohort study based on super-enhancer profiling
Authors: Dongjie Chen, Yizhi Cao, Haoyu Tang, Longjun Zang, Na Yao, Youwei Zhu, Yongsheng Jiang, Shuyu Zhai, Yihao Liu, Minmin Shi, Shulin Zhao, Weishen Wang, Chenlei Wen, Chenghong Peng, Hao Chen, Xiaxing Deng, Lingxi Jiang, Baiyong Shen
Journal: Theranostics (2023)

Rationale: Accumulating evidence illustrated that the reprogramming of the super-enhancers (SEs) landscape could promote the acquisition of metastatic features in pancreatic cancer (PC).Given the anatomy-based TNM staging is limited by the heterogeneous clinical outcomes in treatment, it is of great clinical significance to tailor individual stratification and to develop alternative therapeutic strategies for metastatic PC patients based on SEs.Methods: In our study, ChIP-Seq analysis for H3K27ac was performed in primary pancreatic tumors (PTs) and hepatic metastases (HMs).Bootstrapping and univariate Cox analysis were implemented to screen prognostic HM-acquired, SE-associated genes (HM-SE genes).Then, based on 1705 PC patients from 14 multicenter cohorts, 188 machine-learning (ML) algorithm integrations were utilized to develop a comprehensive super-enhancer-related metastatic (SEMet) classifier.Results: We established a novel SEMet classifier based on 38 prognostic HM-SE genes.Compared to other clinical traits and 33 published signatures, the SEMet classifier possessed robust and powerful performance in predicting prognosis.In addition, patients in the SEMet low subgroup owned dismal survival rates, more frequent genomic alterations, and more activated cancer immunity cycle as well as better benefits in immunotherapy.Remarkably, there existed a tight correlation between the SEMet low subgroup and metastatic phenotypes of PC.Among 18 SEMet genes, we demonstrated that E2F7 may promote PC metastasis through the upregulation of TGM2 and DKK1.Finally, after in silico screening of potential compounds targeted SEMet classifier, results revealed that flumethasone could enhance the sensitivity of metastatic PC to routine gemcitabine chemotherapy.Conclusion: Overall, our study provided new insights into personalized treatment approaches in the clinical management of metastatic PC patients.
Dopamine receptor 1 on CaMKII-positive neurons within claustrum mediates adolescent cocaine exposure-induced anxiety-like behaviors and electro-acupuncture therapy
Authors: Liying Chen, Zhaoyu Liu, Ziheng Zhao, Demin Du, Weichao Pan, Xiaoyan Wei, Jiaxun Nie, Feifei Ge, Jianhua Ding, Yu Fan, Hee Young Kim, Xiaowei Guan
Journal: Theranostics (2023)

Adolescent cocaine exposure (ACE) increases risk of developing psychiatric problems such as anxiety, which may drive relapse in later life, however, its underlying molecular mechanism remains poorly understood.Methods: ACE male mice model were established by exposing to cocaine during adolescent period.Elevated plus maze (EPM) were used to assess anxiety-like behaviors in mice.Within claustrum, local injection of SCH-23390, a specific antagonist for dopamine receptor 1 (D1R), or D1R knocking-down virus were used to regulate D1R function or expression on CaMKII-positive neurons (D1R CaMKII ) in vivo.Electro-acupuncture (EA) treatment was performed at acupoints of Baihui and Yintang during withdrawal period.Results: We found that ACE mice exhibited anxiety-like behaviors, along with more activated CaMKII-positive neurons and increased D1R CaMKII levels in claustrum during adulthood.Inhibiting D1R function or knocking-down D1R CaMKII levels in claustrum efficiently reduced claustrum activation, and ultimately suppressed anxiety-like behaviors in ACE mice during adulthood.EA treatment alleviated ACE-evoked claustrum activation and anxiety-like behaviors by suppressing claustrum D1R CaMKII .Conclusion: Our findings identified a novel role of claustrum in ACE-induced anxiety-like behaviors, and put new insight into the D1R CaMKII in the claustrum.The claustrum D1R CaMKII might be a promising pharmacological target, such as EA treatment, to treat drug-induced anxiety-like behaviors.
Intranasal delivery of mitochondrial protein humanin rescues cell death and promotes mitochondrial function in Parkinson's disease
Authors: Kyung Hwa Kim
Journal: Theranostics (2023)

Rationale: Mitochondrial dysfunction is a key factor in the pathogenesis of Parkinson's disease (PD).Accordingly, many aspects of mitochondrial function have been studied as a putative therapeutic target.Here we present a novel strategy to promote mitochondrial function and protect against Parkinson's disease by the peptide encoded within mitochondrial genome, mitochondria-derived peptide (MDP) humanin (HN).Methods: To test humanin as a potential biomarker in PD, we measured protein levels of circulating humanin from the plasma of PD patients and transgenic or neurotoxic mouse models of PD.Next, we aimed to identify whether HN peptide treatment can regulate its activity or expression.Using mouse models of PD, we assessed HN delivery to the brain via the nasal route of administration.We further revealed a possible mechanism underlying the therapeutic effectiveness of HN peptide for PD using in vitro and ex vivo model of PD.Results: Although the expression of intracellular HN was not correlated with PD, HN treatment itself could induce intracellular HN expression and enhance mitochondrial biogenesis inducing mitochondrial gene expression.After intranasal administration, HN peptide resulted in neuroprotection and behavioral recovery in an animal model of PD.Interestingly, HN peptide following intranasal delivery was found within the brain, mainly via the trigeminal pathways.Mechanistically, HN treatment induced activation of phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) signaling pathway which led to enhanced mitochondrial biogenesis resulting in upregulation of mitochondrial gene including humanin.Conclusion: These data support a novel role of mitochondrial protein humanin in mitochondrial function and neuronal survival against Parkinson's disease, in which humanin treatment is sufficient for stimulating mitochondrial gene expression.
Dietary cobalt oxide nanoparticles alleviate aging through activation of mitochondrial UPR in <i>Caenorhabditis elegans</i>
Authors: Wenshu Cong, Yajie Wang, Chunhui Yuan, Mei Xu, Han Wang, You Hu, Xuyan Dai, Yuhua Weng, Peter Timashev, Xing-Jie Liang, Yuanyu Huang
Journal: Theranostics (2023)

Mitochondrial unfolded protein response (UPR mt ), which is a mitochondrial proteostasis pathway, orchestrates an adaptive reprogramming for metabolism homeostasis and organismal longevity.Similar to other defense systems, compromised UPR mt is a feature of several age-related diseases.Here we report that dimercapto succinic acid (DMSA)-modified cobalt oxide nanoparticles (Co3O4 NPs), which have received wide-spread attention in biomedical fields, is a promising UPR mt activator and, more importantly, provides a gate for extending healthy lifespan.Methods: UPR mt activation by Co3O4 NPs was tested in transgenetic Caenorhabditis elegans (C.elegans) specifically expressing UPR mt reporter Phsp-6::GFP, and the underlying mechanism was further validated by mitochondrial morphology, mtDNA/nDNA, metabolism-related genes' expression, mitonuclear protein imbalance, oyxgen assumption and ATP level in C. elegans.Then therapeutic response aganist senescence was monitored by lifespan analysis, lipofusin contents, MDA contents, Fe accumulation, pharyngeal locomotion performance as well as athletic ability (head thrashes and body bends) at different developmental stages of C. elegans.RNAi towards ubl-5 or atfs-1 in UPR mt pathway was applied to clarify the role of UPR mt in Co3O4 NPs -mediated anti-aging effects.Finally, the effect of Co3O4 NPs on mitochondrial homeostasis and D-galactose-induced cell viability decline in mammalian cells were studied.Results: Co3O4 NPs was revealed as a bona fide activator of the UPR mt signaling pathway, through fine-tuning mitochondrial dynamics and inducing a stoichiometric imbalance between OXPHOS subunits encoded by mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) at early life stage of C. elegans.Phenotypically, Co3O4 NPs treatment protect C. elegans from external stresses.More importantly, dietary low level of Co3O4 NPs effectively extend lifespan and alleviate aging-related physiological and functional decline of worms, demonstrating its potential roles in delaying aging.While the protective effect exerted by Co3O4 NPs was compromised in line with atfs-1 or ubl-5 RNAi treatment.Further studies verified the conservation of Co3O4 NPs in activating UPR mt and exerting protective effects in mammalian cells. Conclusions:The results reveal beneficial effects of Co3O4 NPs on mitochondrial metabolic control, thus presenting their potential efficacy in anti-aging care.
Cell-membrane-coated nanoparticles for the fight against pathogenic bacteria, toxins, and inflammatory cytokines associated with sepsis
Authors: Xiaoyi Wang, Zongping Xia, Huaili Wang, Dao Wang, Tongwen Sun, Eamran Hossain, Xin Pang, Yufeng Liu
Journal: Theranostics (2023)

Sepsis is the main cause of death in patients suffering from serious illness.Yet, there is still no specific treatment for sepsis, and management relies on infection control.Cell membrane-coated nanoparticles (MNPs) are a new class of biomimetic nanoparticles based on covering the surface of synthetic nanoparticles (NPs) with natural cell membranes.They retain the physicochemical properties of synthetic nanomaterials and inherit the specific properties of cellular membranes, showing excellent biological compatibility, enhanced biointerfacing capabilities, capacity to hold cellular functions and characteristics, immunological escape, and longer half-life when in circulation.Additionally, they prevent the decomposition of the encapsulated drug and active targeting.Over the years, studies on MNPs have multiplied and a breakthrough has been achieved for cancer therapy.Nevertheless, the use of "bio"-related approaches is still rare for treating sepsis.Herein, we discussed current state-of-the-art on MNPs for the treatment of bacterial sepsis by combining the pathophysiology and therapeutic benefits of sepsis, i.e., pathogenic bacteria, bacteria-producing toxins, and inflammatory cytokines produced in the dysregulated inflammatory response associated with sepsis.